Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Sample mechanical transport means in or for automated...
Reexamination Certificate
1998-08-14
2002-01-15
Warden, Jill (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Sample mechanical transport means in or for automated...
C422S063000, C422S065000, C422S067000, C422S072000, C422S105000, C436S043000, C436S045000, C436S050000, C436S164000, C436S165000, C436S180000
Reexamination Certificate
active
06338820
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention generally relates to apparatus for performing assays, such as chemical assays and biochemical reactions, or the like, at reaction sites on a substrate. In particular, the invention relates to apparatus for performing assays, such as chemical assays and biochemical reactions by delivering a selected aliquot or selected aliquots to a reaction site or sites on a substrate that may include a plurality of layers of semiconductor material.
2. Description of the Related Art
Until the relatively recent advent of combinatorial chemistry and genetic research spawned the need for high-throughput analyzing and screening techniques, researchers performed such assays using vials, tubes, and beakers. However, with ever more substances available via synthesis or via combinatorial techniques for testing, the need has arisen to test the possible role of thousands, or even millions of substances, in comparable numbers of possible reactions. Miniaturization has been identified as a promising path to more efficient, e.g., less expensive, chemical, and in particular, drug, analysis and screening. Discussions of various aspects of such analysis and screening techniques are found in J. D. Devlin, ed.,
High Throughput Screening: The Discovery of Bioactive Substances
(Marcel Dekker, Inc., New York, 1997); which is incorporated herein by reference to more fully describe the state of the art to which the present invention pertains.
Miniaturization apparatus may be broadly classified into at least two categories. A first category involves the placement of chemical substances in small amounts in sites formed on glass or a similar substrate. Micro-chemistry includes processes carried out in small volumes, e.g., between nanoliter and microliter aliquots, whereby reaction times may be shortened significantly over those conducted in reaction vessels holding on the order a fraction of a milliliter, as currently achievable by a lab technician working “by hand.” In addition to microchemical testing, levels of gene expression may be tested on a large scale.
An example of this first category is the development of microplate technology in which a glass substrate may include site densities of about 10,000 sites. This technology may include the use of complex micro-robotics or the adaptation of ink-jet technology to apply chemical and biochemical substances to chosen sites on the substrates. Frequently, at least one of the reactants in a chemical assay to be performed is chemically linked to or otherwise immobilized at the reaction site. This is done, so that fluids may be added to and removed from the reaction site without removing at least one intermediate or end product of the reaction, which intermediate or end product(s) is (are) to be retained at the reaction site, so that the outcome of the chemical assay may thereby be detected.
Orchid Biocomputer (“Orchid”) of Princeton, N.J., USA, has indicated that it plans to create a credit-card sized glass chip with 10,368 sites. See M. Leach,
Update: Discovery on a Credit Card?,
DRUG DISCOVERY TODAY, 253-4 (Vol. 2, No. 7 (July 1997). For example, each site may cover an area of 100 &mgr;m
2
and may contain less than 1 &mgr;l in volume. The chip is a glass sandwich formed from individual chip layers, which then may be glued together to form tubes to move substances between sites. Such tubes are formed in this device by cutting, e.g., etching, trenches or grooves in a first layer and then sandwiching the trenches under a second layer.
A second category of miniaturization apparatus employs silicon in some functional, e.g., electrical or mechanical, modality as the substrate, and chemicals then are tested on the substrate. In some cases, micro-robotics or micro-chemistry, or both, may be employed with such substrates. For example, Orchid's chip may employ microfluidic pumps, e.g., electronic pumps having no moving parts, to move substances between sites. Nanogen, Inc. also has developed a microelectronic device for handling low-dilutions of charged molecules. However, unlike Orchid, which may use electrokinetic pressure pumping, the Nanogen device employs electrophoresis as a motive agent to analyze chemical reactions acting over the surface of the silicon substrate at about twenty-five reaction sites. Electrokinetic pressure pumping has been described as a combination of electrophoresis and electro-osmosis.
Other research has addressed developing products which employ in-place silicon substrates or devices for chemical testing that include either electrical or micro-mechanical technologies, or both. For example, Synteni, Inc. has developed a process which simultaneously measures the expression of thousands of genes using microscopic cDNA portions placed on a substrate. Synteni also has developed a companion reader that uses two-color fluorescence hybridization detection. Genometrix, Inc. also employs a fluorescence analysis technique that appears similar in concept to the Synteni's process, but carries out the reactions on miniature scale, i.e., on a film that eventually fits over the surface of a reaction reader. Such a reader is manufactured from a silicon chip or wafer modified to function as a photodetector, such as a charge-coupled device (CCD).
Fluorescence generated on the film produces a photocurrent, which provides an electrical charge to a CCD site, and which subsequently may be gated out for analysis, in a manner analogous to the function of a CCD detector array in a digital camera. Thus, known digitizing technology may be combined with the placement of an arrays of chemicals on the surface of a plastic film. The plastic reaction array film may be fitted over the surface of silicon chip or wafer that acts as the reader and when ultra-violet light is flooded over the film surface, fluorescence is elicited from the chemical reaction sites. Each reaction site on the film is aligned with an analyzing site on the reader, and, therefore, a coordinate on the reader corresponds to a reaction site in the chemical array.
Nevertheless, previous attempts to achieve high-throughput analyzing and screening techniques for chemical reactions have required complex operations using combinations of films and substrates or complex robotics for the precise placement of fluids carrying chemical compositions, or both. Such complex systems are subject to failure due to the failure of any system component. Further, such complex systems, especially those including robotics, are expensive to manufacture and maintain.
SUMMARY OF THE INVENTION
Thus, a need has arisen for an efficient, simple to operate, and relatively low cost apparatus for performing a high throughput of chemical assays and biological reactions at reaction sites on a substrate.
A further need has arisen for apparatus which allows high-throughput analyzing and screening techniques for chemical assays of biochemical reactions within an aliquot or between aliquots to be performed at discrete reaction sites. Further, it is a feature of the invention that the delivery of aliquot(s) may be accurately and automatically controlled and monitored, e.g., by a rotatable substrate and a movable fluid dispenser. It is a technical advantage of the invention that etch geometry may be used to form reaction sites which may have added advantages in that they may reduce evaporation and aid in the retention of a portion of the fluid.
Yet a further need has arisen for easily assembled and simply and accurately controlled apparatus for delivering an aliquot or aliquots to reaction sites in order to perform chemical or biochemical testing, or both. It is a feature of the invention that the apparatus achieves a high degree of accuracy in the delivery of fluids to reaction sites. It is a technical advantage of the apparatus that it may employ prepackaged engines or motors, such as linear and rotary stepper motors, to move and position at least one fluid dispenser outlet over a reaction site. Such stepper motors provide a high degree of accuracy and repeatabilit
Hubbard Allyn
Kale Samesh
Rollins Scott A.
Springhorn Jeremy P.
Squinto Stephen P.
Alexion Pharmaceuticals, Inc.
Bex Kathryn
Elrifi Ivor R.
Hopkins Brian P.
Mintz Levin Cohn Ferris Glovsky & Popeo P.C.
LandOfFree
Apparatus for performing assays at reaction sites does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Apparatus for performing assays at reaction sites, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Apparatus for performing assays at reaction sites will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2831491